title: Cutting edge: IL-12 and type I IFN differentially program CD8 T cells for programmed death 1 re-expression levels and tumor control.
abstract: Naive CD8 T cells proliferate in response to TCR and CD28 signals, but require IL-12 or type I IFN to survive and develop optimal effector functions. Although murine CTL generated in vitro in response to IL-12 or IFN-α had comparable effector functions, IL-12-stimulated cells were significantly more effective in controlling tumor in an adoptive immunotherapy model. They maintained high numbers and function, whereas IFN-α-stimulated cells declined in number and became exhausted. Consistent with this, IFN-α-stimulated cells in the tumor expressed higher levels of programmed death 1 (PD-1) inhibitory receptor than did IL-12-stimulated cells. When blocking Ab specific for the PD-L1 ligand of PD-1 was administered, the efficacy of IFN-α-stimulated CTL became comparable with that of IL-12-stimulated cells. Thus, IL-12 and IFN-α differentially program CD8 T cells to re-express distinct levels of PD-1 upon re-encountering Ag, resulting in IL-12-stimulated cells being less susceptible to exhaustion in the face of sustained tumor Ag.
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Gerner
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Heltemes-Harris
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fife
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Mescher
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D007370:Interferon Type I / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007370:Interferon Type I; D016898:Interferon-alpha; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D018664:Interleukin-12